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|Title:||Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria||Authors:||Kang, T.S.
|Keywords:||Enzyme substitution therapy
|Issue Date:||Jan-2010||Citation:||Kang, T.S., Wang, L., Sarkissian, C.N., Gámez, A., Scriver, C.R., Stevens, R.C. (2010-01). Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria. Molecular Genetics and Metabolism 99 (1) : 4-9. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ymgme.2009.09.002||Abstract:||Phenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; second, we used silica sol-gel material as a matrix to demonstrate that a silica matrix can provide protection to entrapped PAL proteins against intestinal proteases, as well as a low pH of 3.5; finally, we demonstrated that PEGylation of AvPAL surface lysines can reduce the inactivation of the enzyme by trypsin. © 2009 Elsevier Inc. All rights reserved.||Source Title:||Molecular Genetics and Metabolism||URI:||http://scholarbank.nus.edu.sg/handle/10635/105778||ISSN:||10967192||DOI:||10.1016/j.ymgme.2009.09.002|
|Appears in Collections:||Staff Publications|
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